(1) Field of the Invention
This invention relates to a method for efficiently producing high-purity 1-(m-ethylphenyl)-1-phenylethane or m-ethylphenylphenylmethane (hereinafter referred to as m-ethyldiphenyls). More particularly, it relates to a method for producing the m-ethyldiphenyls efficiently in a high state of purity which are useful as the raw materials in fields of medicine and organic synthesis.
(2) Description of the Prior Art
.alpha.-Arylpropionic acids which are profen series anodynes have highly antiphlogistic, anti-inflammatory, analgesic and febrifugal effects, and therefore, they are used as drugs. Of these profen series anodynes, .alpha.-(m-benzoylphenyl)propionic acid which is usually called Ketoprofen (trade name) is the good anodyne having high efficacy. For this reason, various producing methods have been suggested in which it is attempted to prepare Ketoprofen inexpensively in a high purity. Of these suggested methods, a method of using the m-ethyldiphenyls as raw materials is considered to be preferable in that a synthetic route is short.
Thus, the method for producing the m-ethyldiphenyls in a high purity which are considered to be preferable as raw materials for the synthesis is demanded, but conventional methods are not always satisfactory, since they cannot synthesize the meta-substituted compound selectively with ease. For example, as methods for synthesizing m-ethylphenylphenylmethane, there are a method of using m-ethylphenol as a starting material in accordance with the Grignard reaction [J. Amer. Chem. Soc., Vol. 76, 5108 (1954)]and other methods, merely preparing a mixture of the aimed product [J. Amer. Chem. Soc., Vol. 84, 1688 (1962) and J. Amer. Chem. Soc., Vol. 91, 7192 (1969)].
Furthermore, as a method for producing 1-(m-ethyl-phenyl)-1-phenylethane, there is a method of obtaining ethyldiphenylethane in the form of a mixture by alkylating diphenylethane with ethylene.
In the above methods which have already been disclosed, the synthesis involves combining complicated multistage reactions and using expensive starting materials, or alternatively the mixture containing ortho-, meta- and para-substituted compounds can be only obtained. That is, the conventional methods require complicated steps toward the intended end product or are inevitably accompanied by the by-product of at least the ortho-substituted compound.
Here, boiling points of the respective ethyl group position isomers of the ethyldiphenyls are shown in the following Tables 1 and 2.
TABLE 1 ______________________________________ Physical Properties of 1-(Ethylphenyl)-1-phenylethanes Substituted Compound Boiling Point (.degree.C.) ______________________________________ Ortho-substituted Compound 285 Meta-substituted Compound 284 Para-substituted Compound 293 ______________________________________
TABLE 2 ______________________________________ Physical Properties of Ethylphenylphenylmethanes Substituted Compound b.p. (.degree.C.) m.p. (.degree.C.) ______________________________________ Ortho-substituted Compound 290.9 -11.2 Meta-substituted Compound 291.5 -9.2 Para-substituted Compound 297.0 -23.5 ______________________________________ (all the b.p.'s are in terms of atmospheric pressure)
As exhibited in the above tables, the ortho- and meta-substituted compounds are substantially similar to each other in physical properties such as the boiling points and melting points, and therefore, any of them cannot be separated from others by a conventional separating means, for example, distillation. If an elaborate separating process is used, the obtained product will be rather expensive and unecomonical. Therefore, it can be concluded that the method in which ortho-substituted compounds are formed as by-products cannot provide the pure meta-substituted compound economically and inexpensively